Trial Outcomes & Findings for The RIME Study - Combined Occipital and Supraorbital Transcutaneous Nerve Stimulation for Treatment of Migraine (NCT NCT03631550)

Last Updated: 2022-09-22

Results Overview

the number and percent of subjects reporting reduction of migraine headache pain 2 hours post treatment initiation from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated migraine attack (if rescue therapy was not used)

Recruitment status

COMPLETED

Study phase

Target enrollment

187 participants

Primary outcome timeframe

2 hours from treatment initiation

Results posted on

2022-09-22

Participant Flow

Participant milestones

Participant milestones
Measure	Active Relivion Active device Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation	Sham Relivion Sham device Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation
Overall Study STARTED	94	93
Overall Study The ITT Analysis Set	67	64
Overall Study The mITT Analysis Set	50	59
Overall Study COMPLETED	67	64
Overall Study NOT COMPLETED	27	29

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The RIME Study - Combined Occipital and Supraorbital Transcutaneous Nerve Stimulation for Treatment of Migraine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active n=67 Participants Relivion Active device Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation	Sham n=64 Participants Relivion Sham device Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation	Total n=131 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	66 Participants n=5 Participants	64 Participants n=7 Participants	130 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	40.7 years STANDARD_DEVIATION 12.47 • n=5 Participants	39.9 years STANDARD_DEVIATION 13.03 • n=7 Participants	40.3 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	51 Participants n=7 Participants	109 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	60 Participants n=5 Participants	57 Participants n=7 Participants	117 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	29 participants n=5 Participants	24 participants n=7 Participants	53 participants n=5 Participants
Region of Enrollment Israel	38 participants n=5 Participants	40 participants n=7 Participants	78 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 hours from treatment initiation

Population: mITT present the number and percentage of subjects with pain relief (reduction in pain level) 2 hours post-treatment, from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated episode. If a subject had used rescue medication up to the assessment time point, he/she was considered as not reaching the endpoint. mITT set included 50 patients in the Active arm and 59 patients in the sham arm

Outcome measures

Outcome measures
Measure	Active n=50 Participants Relivion Active device Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation	Sham n=59 Participants Relivion Sham device Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation
Proportion of Subjects Reporting Reduction of Migraine Headache Pain at 2 Hours From Treatment Initiation	30 Participants	22 Participants

SECONDARY outcome

Timeframe: 2 hours from treatment initiation

Population: mITT population analysis. mITT set included 50 patients in the Active arm from which 36 reported MBS and 59 patients in the sham arm from which 45 reported MBS

The number and percentage of subjects reporting improvement in their Most Bothersome Symptom (MBS) other than a headache, 2 hours post-treatment initiation (if rescue therapy was not used), in their first eligible treated migraine attack. MBS may be nausea, photophobia, phonophobia

Outcome measures

Outcome measures
Measure	Active n=36 Participants Relivion Active device Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation	Sham n=45 Participants Relivion Sham device Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation
Proportion of Subjects Reporting Improvement in Their Most Bothersome Symptom (MBS) Other Than a Headache, 2 Hours Post-treatment Initiation	29 Participants	27 Participants

SECONDARY outcome

Timeframe: 1 hour from treatment initiation

Population: mITT population analysis. mITT set included 50 patients in the Active arm and 59 patients in the sham arm

The number and percentage of subjects reporting reduction of migraine headache pain 1-hour post treatment initiation (if rescue therapy was not used), from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated migraine attack

Outcome measures

Outcome measures
Measure	Active n=50 Participants Relivion Active device Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation	Sham n=59 Participants Relivion Sham device Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation
Proportion of Subjects Reporting Reduction of Migraine Headache Pain 1-hour Post Treatment Initiation	21 Participants	15 Participants

SECONDARY outcome

Timeframe: 2 hours from treatment initiation

Population: mITT population anaylsis. mITT set included 50 patients in the Active arm and 59 patients in the sham arm

The number and percentage of subjects who are pain free at 2 hours post treatment initiation (if rescue therapy was not used), in their first eligible treated migraine attack

Outcome measures

Outcome measures
Measure	Active n=50 Participants Relivion Active device Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation	Sham n=59 Participants Relivion Sham device Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation
Proportion of Subjects Who Are Pain Free at 2 Hours Post Treatment Initiation	23 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Enrollment (randomization) through study exit i.e. 70 days

Population: ITT population analysis

Safety of the study device following study treatment: Number and Rate of participates with Adverse events related or unrelated to the study device

Outcome measures

Outcome measures
Measure	Active n=67 Participants Relivion Active device Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation	Sham n=64 Participants Relivion Sham device Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation
Number of Participants With Adverse Events Participants with device related Adverse Events	5 Participants	2 Participants
Number of Participants With Adverse Events Participants with Adverse Events	8 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline to 1-hour post treatment

Population: mITT set included 50 patients in the Active arm and 59 patients in the sham arm

as per the Statistical Considerations for Clinical Trials During the COVID-19 Public Health Emergency" June 2020 FDA Guidance, which states that a modifications to the definition and ascertainment of trial endpoints may be warranted to address the impact of COVID-19. A potential modification for a binary endpoint that is based on a continuous or ordinal measurement is by using the continuous or ordinal measurement as the endpoint. therefore, an additional analysis to the study end points , the migraine headache pain level was transformed into a numerical score (pseudo-continuous): "No pain"=0, "Mild"=1, "Moderate"=2, "Severe"=3. If rescue medication was used, the score after the rescue intake post-treatment are set to the baseline value. The change from baseline is compared between the study arms with an analysis of covariance model adjusted for site and baseline pain level.

Outcome measures

Outcome measures
Measure	Active n=50 Participants Relivion Active device Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation	Sham n=59 Participants Relivion Sham device Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation
The Change in Pseudo-continuous Pain Score From Baseline to 1-hour Post Treatment	-0.637 units on a scale Interval -0.881 to -0.392	-0.306 units on a scale Interval -0.537 to -0.075

Adverse Events

Active

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Sham

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Active n=67 participants at risk Relivion Active device Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation	Sham n=64 participants at risk Relivion Sham device Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation
Nervous system disorders Migraine	1.5% 1/67 • Number of events 2 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	0.00% 0/64 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Nervous system disorders Unpleasant sensation during treatment	1.5% 1/67 • Number of events 1 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	1.6% 1/64 • Number of events 3 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Nervous system disorders Scalp numbness sensation	1.5% 1/67 • Number of events 1 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	0.00% 0/64 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Nervous system disorders Pain	1.5% 1/67 • Number of events 2 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	0.00% 0/64 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Skin and subcutaneous tissue disorders Skin redness	0.00% 0/67 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	1.6% 1/64 • Number of events 3 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Nervous system disorders Tingling	1.5% 1/67 • Number of events 1 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	0.00% 0/64 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Nervous system disorders Twitching	1.5% 1/67 • Number of events 1 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	0.00% 0/64 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Infections and infestations COVID	1.5% 1/67 • Number of events 1 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	0.00% 0/64 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Infections and infestations upper respiratory infection	1.5% 1/67 • Number of events 1 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	0.00% 0/64 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Ear and labyrinth disorders inner ear scratch	1.5% 1/67 • Number of events 1 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	0.00% 0/64 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
General disorders lip numbness	1.5% 1/67 • Number of events 1 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	0.00% 0/64 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.
Nervous system disorders Pressure/discomfort of head	0.00% 0/67 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.	1.6% 1/64 • Number of events 3 • Adverse events data were collected per study participant from Enrollment (randomization) through study exit. ie 70 days Adverse events related or unrelated to the study device and/or procedure were collected per study participant from Enrollment (randomization) through study exit. The ITT data analysis set served as the principal data analysis set for the safety analyses.

Additional Information

Michal Kedar-Datel

Neurolief Ltd.

Phone: +972-52-6659806

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place